Tooth decay, or dental caries, initially results in the demineralization, and ultimately, in the complete destruction of tooth enamel and the underlying dentin. Currently, the restoration of carious teeth typically involves removing the demineralized enamel and dentin, followed by the placement of dental restoratives such as silver amalgams, cast gold inlays, ceramics, composite resins, and various organic polymers. However, despite major technological advances that have significantly improved the clinical performance of dental composite resins and ceramics, no current method of restoring teeth completely joins the alloplastic restorative material to the remaining mineralized natural tooth structure. Indeed, many dental restorations will ultimately fail because bacteria will penetrate this junction, leading to a condition known as recurrent caries.
Enamel is the hardest substance produced by a mammal's body. In mammals, the enamel layer of a tooth is formed during embryogenesis from protein secretions from ameloblast cells. As the tooth erupts, the layer of ameloblast cells is shed, and no more enamel can be naturally produced. Many groups have studied the formation of enamel and have attempted to imitate enamel formation and mineralization through various tissue engineering techniques.
There are two major groups of proteins found in the developing extracellular matrix (“ECM”) of enamel: amelogenins and enamelins. The amelogenins constitute 90% of the ECM proteins and are lost during mineralization. Deutsch et al., J. Biol. Chem. 266:16021-16028 (1991). Conversely, the enamelins constitute only a minor fraction of the ECM proteins, but are partially retained in mature dental tissue. The acidic nature of enamelins (they include glutamic acid, aspartic acid, serine, and glycine residues), as well as their beta-pleated sheet structure, suggests a role in nucleation and regulation of enamel crystal growth. Recognizing this, U.S. Pat. No. 4,672,032 to Slavkin et al. provides methods for the formulation of dental enamel crystals in a biosynthetic matrix by the nucleation of calcium solutions with enamel proteins, and for the use of these enamel crystals as a dental restorative material. The methods assume the carious lesion does not extend into the tooth structure beyond the dentin/enamel junction (“DEJ”). In addition, the method does not provide for a rigid support capable of sustaining masticatory forces until the nascent enamel eventually becomes mineralized.
U.S. Pat. No. 5,071,958 to Hammarstrom et al. describes a process utilizing enamel matrix proteins for inducing binding between parts of living mineralized tissue by regeneration of mineralized tissue on at least one of the parts. Similar to Slavkin et al., however, the enamel matrix proteins are not applied within a rigid support, and are therefore unable to withstand masticatory crushing forces.
Recent advances in calcium phosphate chemistry have produced dental composite formulations that promise to remineralize demineralized enamel, dentin and cementum. See, U.S. Pat. No. 6,398,859 to Dickens et al., for example. These compounds are able to react with water to release calcium phosphate with release kinetics predicted to produce hydroxyapatite or fluoroapatite. However, the released mineral does not remain associated with the composite, but is instead deposited on the tooth surface. Currently, there is no known dental restorative material that has the ability to incorporate or form highly ordered mineral, such as hydroxyapatite or fluoroapatite, after placement, thereby sealing the junction between the restorative material and adjacent dental tissue.
The present invention is directed to overcoming these and other deficiencies in the art.